The recently released sequences
from Chihuahua, Mexico have raised concerns that the re-emerging
sub-clade would rapidly spread and cause more severe
disease. The sub-clade has one receptor binding domain (RBD)
change, A189T, as well as three additional non-synonymous changes
(N34D, S165N, and V275I).

The concerns were increased by the presence of D225N in the sequence, A/Mexico/InDRE1945/2011, from a fatal case (36M). This case
was part of a cluster in the traffic department in Juarez. The
partner of the above case also died, and a third co-worker was in
critical condition, raising concerns that the D225N was linked to this
cluster and c`ause the severe and fatal cases.

The above sub-clade was seen in a small number of human
cases in the US in the spring of 2010. However, in addition
to the spring cases, one isolate from August, A/Pennsylvania/07/2010,
was more closely related to the Chihuahua sub-clade. The clinical
status of the case (23F) was not known, but the sequence has
D225G. Previously, sequences from autopsy lung samples collected
in Ukraine in 2009 had a high frequency of D225G and D225N, raising
concerns that the emergence of a sub-clade with a high frequency of
isolates with these changes would lead to an increase in severe and
fatal case.

Moreover, these changes may lead to immunological escape which would
drive the spread of this sub-clade.

The current extent of spread in the US is not known. Recently the
Air Force released 2011 H1N1 sequences from military personnel and
dependents. This sub-clade was present in cases found throughout
the US (NJ, NC, SC, FL, AZ). However, sequences from Texas were
not released by the Air Force, and the CDC has withheld
the release of 2011 isolates from patients throughout the US.
Epimiological data links the outbreak in Chihuahua with travel from New
Mexico and Texas.

The sub-clades with A189T and an additional change at position 225
(D225G or D225N) have parallels with the emergence of H3N2 with
adamantine resistance. The H3N2 sub-clade was characterized by
S193F and D225G. Moreover, the co-circulation of the S188T and
A189T sub-clades could lead to sequences with both RBD changes, which
have been seen in recent sequences from North Carolina (A/North
Carolina/AF21793/2010) and the country of Georgia (A/Georgia/51/2011).

Therefore release of 2011 sequences from severe and fatal cases in the
United States, as well as Mexico and Venezuela is overdue.